| Project/Area Number |
16591358
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Toho University |
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Principal Investigator |
HEMMI Hiromichi Toho Univ., Dept.Mol.Biol., Associate professor, 医学部, 助教授 (90165514)
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| Co-Investigator(Kenkyū-buntansha) |
KOIKE Junichi Toho Univ., Dept.Surg, Research associate, 医学部, 助手 (30339155)
ARITA Michitsune Toho Univ., Dept.Mol.Biol., Research associate, 医学部, 助手 (80307719)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2004: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | colorectal carcinoma / DNA mismatch repair / molecular genetic marker / microsatellite instability / LOH / EMAST / drug sensitivity / DNA double-strand breaks / DNAミスマッチ修復 / 遺伝性非ポーリープ性大腸癌 / マクロサテライト不安定性 / 抗癌薬感受性 / 散発性大腸癌 / ゲノム不安定性 |
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| Research Abstract |
Defect in the DNA mismatch repair (MMR) system evokes a microsatellite instability (MSI) phenotype and Multi-drug resistant phenotype including 5-FU and its derivertives. Recent accumulating evidences in the tumor suggest that establishment of chemotherapuetic regimen specified for the MMR-deficient tumor may be possible. Establishment of easy procedure for determining MSI tumor and search the hypersensitive anticancer agent to MMR-deficient tumor may be urgent. In this study, we mainly investigated following two categories :
1.Studies using molecular genetic marker
Genomic instability such as MSI, LOH, and EMAST using the specific locus markers was investigated in 70 sporadic colorectal cancer. Eleven MSI tumors (4 MSI-H and 7 MSI-L) and 39 EMAST-positive tumors were found. All MSI tumors showed EMAST. However, pattern of MSI-H was differ from a typical pattern of EMAST, indicate that generative mechanism of the MSI -and EMAST tumors is different. Since requency of LOH in EMAST tumors is relatively higher than EMAST-negative tumors, EMAST is a part of CIN tumor.
2.Mode of action of the hypersensitive drugs to MMR-deflcient human colorectal carcinoma cell lines. MMR proteins prevent DNA double-strand breaks induced by DNA polymerase inhibitors.
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